title: Brain damage by mild metabolic derangements in methylmalonic acidemia.
abstract: Methylmalonic acidemia caused by an l-methylmalonyl-CoA mutase deficiency. The mut(0) type is associated with significant mortality and morbidity, but tandem mass spectrometry has made early detection possible. Five patients were identified through newborn screening for elevated propionylcarnitine (C3-carnitine) levels. These patients received a positive screening result at a median age of 10 days (range, 5-18 days). When treated at a median age of 11 days (range, 3-50 days), 2 patients were asymptomatic, and only one was significantly acidotic (pH <7.2), but all had various degrees of hyperammonemia (range, 127-1,244 mumol/L). Magnetic resonance imaging of the brain was performed in 4 patients shortly after diagnosis, and the results were all abnormal. Four patients were followed. There was no further metabolic decompensation after the initial episodes, but their mean developmental quotient was only 50. These results suggest that early hyperammonemia can lead to significant brain damage in methylmalonic acidemia. Therefore, treatment of this disease in newborns must be more aggressive.
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ni-Chung
authors.initials: NC
authors.lastname: Lee
authors.forename: Yin-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Shinn-Forng
authors.initials: SF
authors.lastname: Peng
authors.forename: Ai-Chu
authors.initials: AC
authors.lastname: Huang
authors.forename: Tze-Tze
authors.initials: TT
authors.lastname: Liu
authors.forename: Ariel Sing-Huei
authors.initials: AS
authors.lastname: Wu
authors.forename: Li-Chu
authors.initials: LC
authors.lastname: Chen
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.forename: Shih-Chuan
authors.initials: SC
authors.lastname: Tseng
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002675:Child, Preschool; D006801:Humans; D022124:Hyperammonemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008661:Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008764:Methylmalonic Acid / Q000097:blood; D008765:Methylmalonyl-CoA Mutase / Q000172:deficiency* / Q000235:genetics; D015997:Neonatal Screening; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D008764:Methylmalonic Acid; D008765:Methylmalonyl-CoA Mutase